JP2836544B2 - Method for producing polycondensate of amino acid and biodegradable polypeptide hydrolyzate thereof - Google Patents

Abstract

Prodn. of amino acid polycondensates or their polypeptide hydrolysates comprises subjecting an homogeneous powdered mixt. of amino acid and catalyst to thermal polycondensation and opt. hydrolysing the prod. The catalyst is H3PO4, P2O5 or polyphosphoric acid (PPA). The molar ratio of catalyst to amino acid is 0.005-0.25:1, pref. 0.01-0.18:1.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION This invention relates to the process of the invention by hot polycondensation of amino acids in finely divided media in the presence of small amounts of phosphoric acid, phosphorus pentoxide or polyphosphoric acid, followed by optional hydrolysis.
The present invention relates to a method for producing a polycondensate of an amino acid or a hydrolyzate of a biodegradable polypeptide thereof (that is, a biodegradable polypeptide produced by hydrolysis thereof).

[0002]

BACKGROUND OF THE INVENTION It is known to produce polyanhydroaspartic acid by thermal polycondensation of aspartic acid in the presence of phosphoric acid, phosphorus pentoxide or polyphosphoric acid. It has been proposed to operate under atmospheric pressure in order to obtain polysuccinimide of limited molecular weight and under reduced pressure in order to obtain polysuccinimide of high molecular weight.

[0003] SW Fox and K. Harada, in the atmospheric pressure H ₃ H at 180 ° C. in the presence of PO _{4 3} PO ₄ /
The maximum yield is obtained at a molar ratio of aspartic acid of 3/4, and in the case of a 2/1 molar ratio of aspartic acid / glutamic acid mixture, at a molar ratio of H ₃ PO ₄ / (aspartic acid + glutamic acid) of 2/3. Teaches the best results. Pergamon Pre, Elmsford, NY, USA
ss), A Laboratory Manual of AnalyticalMethods o
f Protein Chemistry, including Polypeptides (19
66, p. 129｝.

[0004] SW Fox and K. Harada also disclose in US Pat. No. 3,052,655 a 1: 1 molar ratio of aspartic acid / glutamic acid mixture in equimolar amounts of H ₃ PO.
It has also been proposed to carry out polycondensation in the presence of ₄ under atmospheric pressure at a temperature of 150-210 ° C.

[0005] French patent no.
It is described that aspartic acid is condensed in a thin layer under reduced pressure in the presence of H ₃ PO _{4 at} a temperature of 170-200 ° C. according to a weight ratio of 85% H ₃ PO ₄ / aspartic acid 0.5. .

[0006] P. Neri, G. Antoni, F. Benvenuti, F.
Cocola and G. Gazzei describe polysuccinimides obtained by polycondensation of H ₃ PO ₄ / aspartic acid in a thin layer at 180 ° C. under reduced pressure in a thin layer at a molar ratio ranging from 0.4 / 1 to 2/1. The effect of the molar ratio of H ₃ PO ₄ / aspartic acid on the viscosity was studied (Journal of Med.
icinal Chemistry, 1973, Vol. 16, No. 8).

[0007] East German Patent No. 262665 discloses that aspartic acid has a polyphosphoric acid / aspartic acid ratio of 1/3 to 2
The polycondensation is described in the presence of polyphosphoric acid at a temperature of 160 to 200 ° C. under vacuum.

[0008] French Patent No. 2665166 states that
The aspartic acid is converted to phosphoric acid, phosphorus pentoxide or polyphosphoric acid / aspartic acid in a ratio of 0.1 / 1 to 2/1, preferably 0.3 /
It has been proposed to produce very high molecular weight polysuccinimides by polycondensation at 100-250 ° C. under vacuum in the presence of phosphoric acid, phosphorus pentoxide or polyphosphoric acid according to 1-1 / 1. The operation is performed in two steps, the first one consisting of preparing a polysuccinimide having a molecular weight of 10,000-100,000.
The second operation mechanically destroys the hard, solidified reaction medium,
Consisting of continuing the polycondensation.

[0009]

All of these methods have the disadvantage of using large amounts of phosphoric acid or polyphosphoric acid (to be subsequently removed), and the reaction medium must pass through a more or less viscous phase. The disadvantage is that a considerable amount of foam is formed (the foam needs to be broken) and at the end of the polycondensation the medium agglomerates (needs final grinding). There is also. Such a method is difficult to implement industrially.

The Applicant has found a process which makes it possible to use less than 40 mol% of phosphoric acid, phosphorus pentoxide or polyphosphoric acid, without foaming and without coagulation of the reaction medium. Was.

[0011]

SUMMARY OF THE INVENTION The present invention provides a method for the polycondensation of amino acids by bulk thermal polycondensation of amino acids in the presence of phosphoric acid, phosphorus pentoxide or polyphosphoric acid as a polycondensation catalyst, followed by optional hydrolysis. A method for producing a condensate or a polypeptide hydrolyzate thereof, wherein 0.07
About 0.05 to 0.25 mol, preferably 0.01 to 0.1 mol
The present invention relates to the above method, wherein the polycondensation operation is performed in a finely divided medium in which about 8 mol of a catalyst is uniformly dispersed.

In defining the number of moles of the catalyst, the molecule in the case of phosphoric acid and the P in the case of phosphorus pentoxide or polyphosphoric acid are used.
The number of moles is determined by taking atoms into consideration (P
One atom is equivalent to one molecule of phosphoric acid). In defining the number of moles of amino acids, the number of moles is determined taking the molecule into consideration.

[0013]

DETAILED DESCRIPTION OF THE INVENTION Examples of amino acids that can be used in carrying out the method of the present invention include aspartic acid or glutamic acid alone, or a mixture thereof in any proportion, or one or both of them. (Eg up to 15% by weight, preferably up to 5% by weight of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, histidine, proline, lysine, serine, threonine, cysteine, etc.) Can be mentioned. The preferred amino acid is aspartic acid.

The thermal polycondensation operation can be performed at a temperature of about 150 to 22 ° C., preferably at a temperature of about 180 to 200 ° C. This operation can be performed at a selected constant temperature or according to a pre-established temperature distribution.
This thermal polycondensation operation can be carried out under vacuum (preferably 1 mbar or more), at atmospheric pressure or optionally under pressure (for example up to 20 bar), depending on the desired molecular weight. As a means for introducing the catalyst, any means for introducing the catalyst in the above-mentioned ratio and enabling to obtain a fine powder mixture in which the catalyst is uniformly dispersed can be used.

In a possible embodiment of the invention, a finely divided reaction medium containing a homogeneously dispersed catalyst which is subjected to a polycondensation operation comprises: a paste of a mixture of amino acids and phosphoric or polyphosphoric acid with water. Dissolving the amino acids and phosphoric acid or polyphosphoric acid in water, preferably hot water, by removing the water by evaporating and evaporating at atmospheric pressure or preferably under vacuum, and then grinding the resulting body; Then by spraying this solution; by spraying a suspension of the amino acid in an aqueous solution of phosphoric acid or polyphosphoric acid; by evaporating the aqueous solution of phosphoric acid or polyphosphoric acid on a fluidized bed of amino acids; or -Examples include those obtained by co-milling or finely grinding phosphorus pentoxide and amino acids.

A particularly advantageous embodiment is to use phosphoric acid or polyphosphoric acid as catalyst, introducing the phosphoric acid or polyphosphoric acid into the amino acids, and mixing the mixture in an amount sufficient to obtain a homogeneous paste-like medium (preferably 1 amino acid per weight). 0.4 to 1 per part
(Parts by weight) and homogenized by making into a paste with water, and removing excess water from the mixture by drying at atmospheric pressure or preferably under vacuum (typically below 10,000 Pa). Comminuted body to obtain a finely divided medium, and then performing a polycondensation operation. The term "excess water" shall mean water which is not in equilibrium with phosphoric acid or polyphosphoric acid at the drying temperature and pressure.

The polyimide obtained according to the process of the present invention can be separated, filtered, purified and dried, if necessary. The catalyst can be separated from the polyimide, if desired, by washing with water or by using a solvent that is a solvent for the catalyst and a non-solvent for the polyimide. The polyimide is purified by dissolving it using a polar aprotic solvent (dimethylformamide, formamide, dimethylsulfoxide, etc.) and then reprecipitating it using a non-solvent compound for polyimide (water, ether, ethanol, acetone, etc.). can do.

The resulting polyimide, separated or unseparated, is then hydrolyzed, preferably in a homogeneous or two-phase medium, if necessary, in the presence of water in a homogeneous or two-phase medium (alkali metal or alkali). (E.g., an earth metal base, an alkali metal or an alkaline earth metal carbonate). In the case of polysuccinimide derived from aspartic acid, the hydrolyzate thus obtained consists of polyaspartate (eg sodium polyaspartate).

The acid form of the hydrolyzate can be obtained, for example, by neutralizing the salt obtained by alkaline hydrolysis with an organic or inorganic acid (in particular HCl). In the case of polysuccinimide derived from aspartic acid, the hydrolyzate thus obtained consists of polyaspartic acid.

According to the present invention, the term "hydrolysate" means a partial or complete hydrolysis (by the action of water) of the formed polyimide. This hydrolysis leads to the formation of amide functions on the one hand and carboxylic acid functions or carboxylate salts on the other hand, by ring opening of the imide ring.

The products obtained according to the invention are, in particular,
Biodegradable polypeptide "builder" or "cobuilder" agent in a cleaning composition (laundry cleaning product, dishwashing product or any other household cleaning product) (enhancing surfactant performance) Additives or auxiliaries).

[0022]

The following examples are given as a guide. Measurement of viscosity index (VI) Viscosity index (VI) given in these examples
Is obtained by dissolving polysuccinimide (PSI) in 0.5 N sodium hydroxide at a temperature of 25 ° C. in an amount to give a concentration of 0.002 g / milliliter using a SCHOTT AVS 350 capillary viscometer. Viscosity index VI1) or • Measured from a solution of polysuccinimide (PSI) dissolved in dimethylformamide at a temperature of 25 ° C. in an amount to give a concentration of 0.005 g / milliliter (viscosity index VI2).

Determination of Biodegradability of Hydrolyzate In these examples, the biodegradability of the hydrolyzate was
AFNOR standard T90-312 (October 15, 1984
According to the Japanese International Standard ISO-7827). The test was performed using the following. • Inoculum (as is or prepared) obtained by filtering the inlet water of a public water purification plant at Saint Germain auMont d'Or, Rh ロ ー ne, France. • Per milliliter. Test medium containing 4 × 10 ⁵ bacteria Test compound in an amount such that the test medium contains a concentration of about 40 ml / g organic carbon. The degree of biodegradation was measured as a function of time under conditions discharged into river water. The test sample for this measurement was prepared by hydrolyzing the produced polysuccinimide with a dilute sodium hydroxide solution until an about 6% sodium polyaspartate solution having a pH of about 9 to 11 was obtained. ,Obtained. The level of biodegradability is characterized by two parameters: • Maximum biodegradability (MRB) • Time required to reach 90% biodegradation from 10% of maximum biodegradability ( _T10-90 ).

Hunter L. a. b. Obey the law
Color measurement The color of polysuccinimide powder or its hydrolyzate is AC
Determined by measurement using a S SPECTRO-SENSOR II® spectrocolorimeter. The measurement conditions are as follows. Light source: D65 Observation angle: 2 ° The following three values were measured. L: luminance. This varies from 0 (black) to 100 (white). A: Red to green hue. When a is a positive (+) value, it indicates that there is a tendency toward red, and when a is a negative (−) value, it indicates that there is a tendency toward green. B: yellow to blue hue. When b is a positive (+) value, it indicates a tendency to yellow, and when b is a negative (-) value, it indicates a tendency to blue. These values are calculated from measurements according to the following formula: L = 100 (Y / Y ₀ ) ^1/2 a = K _a (X / X ₀ −Y / Y ₀ ) / (Y / Y ₀ ) ^1/2 b = K _b (Y / Y ₀ −Z / Z ₀ ) / (Y / Y ₀ ) ^1/2 where X, Y and Z are the tristimulus values corresponding to the three primary colors obtained for the sample, and X ₀ , Y ₀ and Z ₀ are the light sources used. tristimulus values for the complete diffuser of, K _a
And K _b are coefficients of the light source used.

Example 1 A finely divided reaction mixture is prepared by the following procedure: 8 g of 400 g of L-aspartic acid on an enamel coated plate
The medium is homogenized by adding 20 g of 5% orthophosphoric acid and pasting with 320 g of water, then in an oven under vacuum at 40 ° C., 6000 Pa
The water is evaporated to dryness for 16 hours at 80 ° C. and 6000 Pa for 21 hours, and 416.7 g of the mixture obtained are ground using an impact disc mill (broyeur a couteaux with a blade). 51.8 g of this finely powdered mixture are introduced into a 250 ml rotary evaporator flask which has been preheated to 200 ° C. (oil bath temperature). The flask is rotated at a speed of 20 rpm. After 4 hours of polycondensation at 200 ° C. under atmospheric pressure, 42.0 g of product are recovered without washing with water, which corresponds to a polyanhydroaspartic acid (polysuccinimide PSI) yield of 72.0%. (Confirmed by potentiometric analysis). Agglomeration of reactants during polycondensation operation
(mottage) was not identified. The product had a viscosity index VI1 of 13.6 ml / g and the following Hunter color. -L = 91.2-a = 1.3-b = 10.2

Example 2 A finely powdered reaction mixture is prepared by the following procedure: 8 g of 800 g of L-aspartic acid on an enamel coated plate
The medium is homogenized by adding 80 g of 5% orthophosphoric acid and pasting with 640 g of water, then in an oven under vacuum at 40 ° C., 6000 Pa
The water is evaporated to dryness for 20 hours at 80 ° C. and 6000 Pa for 25 hours and then at 80 ° C. and 650 Pa for 2 hours. 867.9 g of the mixture obtained are subjected to impact disc milling (milling with a blade). And crush. 53.4 g of this finely powdered mixture are introduced into a 250 ml rotary evaporator flask which has been previously heated to 200 ° C. (oil bath temperature). The flask is rotated at a speed of 20 rpm. After 4 hours of polycondensation at 200 ° C. and atmospheric pressure, 41.0 g of product are recovered without washing with water, which corresponds to a 92.0% yield of polyanhydroaspartic acid (polysuccinimide PSI). (Confirmed by potentiometric analysis). No coagulum of the reactants was observed during the polycondensation operation. The product is 15.7 ml /
g and had the following Hunter color: -L = 90.7-a = 0.4-b = 10.8 This polysuccinimide was hydrolyzed as described above. The biodegradability of this hydrolyzate was as follows.・ MRB = 97% ・ t _10-90 = 7 days

Example 3 A finely divided reaction mixture is prepared by the following procedure: In a rotary evaporator equipped with a 250 ml flask, 50 g of L-aspartic acid and 85% orthophosphoric acid 7.
The medium is homogenized by adding 5 g and pasting with 21 g of water, and then in a rotary evaporator under vacuum at 80 ° C., 46
The water is evaporated to dryness at 00 Pa for 35 minutes and then at 1300 Pa for 4 hours.-Grind 56.3 g of the resulting mixture using a mortar. 55.2 g of this pulverulent mixture are introduced into a 250 ml rotary evaporator flask which has been preheated to 200 ° C. (oil bath temperature). The flask is rotated at a speed of 20 rpm. After 4 hours of polycondensation at 200 ° C. and atmospheric pressure, 42.3 g of product are recovered without washing with water, which corresponds to a 100% yield of polyanhydroaspartic acid (polysuccinimide PSI) ( Confirmed by potentiometric analysis). At the beginning of the polycondensation, the media was observed to agglomerate, which was removed by scraping the reactants. Thereafter, the test was developed in a pulverulent medium without coagulation. The product had a viscosity index VI1 of 14.7 ml / g and the following Hunter color.・ L = 90.4 ・ a = -0.7 ・ b = 11.1

Example 4 A finely divided reaction mixture is prepared by the following procedure: In a rotary evaporator equipped with a 250 ml flask, 50 g of L-aspartic acid and 85% orthophosphoric acid.
The medium is homogenized by adding 5 g and making into a paste with 20 g of water, and then at 80 ° C. under vacuum in the rotary evaporator at 60 ° C.
The water is evaporated to dryness at 00 Pa for 20 minutes and then at 1300 Pa for 4 hours.-52.2 g of the resulting mixture are ground in a mortar. 51.9 g of this fine powder mixture is introduced into a 1 liter rotary evaporator flask which has been heated to 200 ° C. (oil bath temperature) in advance. The flask is rotated at a speed of 20 rpm.
After 6 hours of polycondensation at 180 ° C. and atmospheric pressure, 44.0 g of product are recovered without washing with water, which corresponds to a 60% yield of polyanhydroaspartic acid (polysuccinimide PSI) ( Confirmed by potentiometric analysis). No coagulum was found during the polycondensation. The product had a viscosity index VI2 of 12.9 and the following Hunter color. L = 93.3 a = 0.3 b = 8.2

Example 5 A finely divided reaction mixture is prepared by the following procedure: In a rotary evaporator equipped with a 250 ml flask, 50 g of L-aspartic acid and 85% orthophosphoric acid 5.
The medium is homogenized by adding 0 g and making into a paste with 20 g of water, then at 80 ° C. under vacuum in the rotary evaporator at 80 ° C.
1 hour 20 minutes at 00Pa, then 1300Pa
Evaporate the water for 2 and a half hours to dry and pulverize 54.3 g of the mixture obtained using a mortar. 53.8 g of this finely divided mixture are introduced into a 250 ml rotary evaporator flask which has been heated to 200 ° C. (oil bath temperature) in advance. The flask is rotated at a speed of 20 rpm. After 6 hours of polycondensation at 180 ° C. and atmospheric pressure, 42.0 g of product are recovered without washing with water, which corresponds to a 91% yield of polyanhydroaspartic acid (polysuccinimide PSI) ( Confirmed by potentiometric analysis). No coagulum was found during the polycondensation. The product had a viscosity index VI1 of 13.9 and the following Hunter color. -L = 94.1-a = -0.9-b = 7.2 This polysuccinimide was hydrolyzed as described above. The biodegradability of this hydrolyzate was as follows.・ MRB = 94% ・ t _10-90 = 5 days

Example 6 A finely divided reaction mixture is prepared by the following procedure: 50 g of L-aspartic acid and 85% orthophosphoric acid in a rotary evaporator equipped with a 250 ml flask 7.
The medium is homogenized by adding 5 g and making into a paste with 20.3 g of water, then at 80 ° C. under vacuum in the rotary evaporator, at 46 ° C.
Evaporate the water for 30 minutes at 00 Pa and then for 4 hours at 650 Pa.-Grind 56.6 g of the resulting mixture using a mortar. 55.4 g of this finely divided mixture are introduced into a 250 ml rotary evaporator flask which has been heated to 200 ° C. (oil bath temperature) in advance. The flask is rotated at a speed of 20 rpm. After 6 hours of polycondensation at 180 ° C. under atmospheric pressure, 42.9 g of product are recovered without washing with water, which corresponds to a 97% yield of polyanhydroaspartic acid (polysuccinimide PSI) ( Confirmed by potentiometric analysis). At the beginning of the polycondensation, the media was observed to agglomerate, which was removed by scraping the reactants. Thereafter, the test was developed in a pulverulent medium without coagulation. The product had a viscosity index VI1 of 14.7 and the following Hunter color. L = 92.8 a = -0.9 b = 8.8

Example 7 A finely divided reaction mixture is prepared by the following procedure: L- in a rotary evaporator equipped with a 3 liter flask
The medium is homogenized by adding 20 g of 85% orthophosphoric acid to 400 g of aspartic acid and pasting with 320 g of water, then: in a rotary evaporator under vacuum at 80 ° C. under 26
Evaporate the water at 00 Pa for 1 hour, then at 1300 Pa for 4 hours and 15 minutes, then further dry in an oven at 80 ° C. at 6600 Pa for 65 hours. Grind 413 g of the resulting mixture using a mortar. 50 g of this finely powdered mixture was previously prepared at 200 ° C. (oil bath temperature).
Into a heated 250 ml rotary evaporator flask. The flask is rotated at a speed of 20 rpm. After 6 hours of polycondensation under vacuum (1300 Pa) at 180 ° C., the product 39.7 without washing with water.
g are recovered, which corresponds to a 79% yield of polyanhydroaspartic acid (polysuccinimide PSI) (confirmed by potentiometric analysis). No coagulum was found during the polycondensation. The product had a viscosity index VI1 of 33.6 and the following Hunter color. -L = 89.7-a = 0.8-b = 13.5

Example 8 A finely divided reaction mixture is prepared by the following procedure: 50 g of L-aspartic acid and 85% orthophosphoric acid in a rotary evaporator equipped with a 250 ml flask 7.
The medium is homogenized by adding 8 g and making into a paste with 20 g of water, then in a rotary evaporator under vacuum at 80 ° C., 46
Evaporate the water at 00 Pa for 35 minutes and then at 1300 Pa for 4 hours. • Grind 56.3 g of the resulting mixture using a mortar. 55.5 g of this finely divided mixture are introduced into a 250 ml rotary evaporator flask which has been heated to 200 ° C. (oil bath temperature) in advance. The flask is rotated at a speed of 26 rpm. 200 ° C. under vacuum (1300 Pa)
After a polycondensation for a time, the product 4 is obtained without washing with water.
1.8 g are recovered, which corresponds to a 100% yield of polyanhydroaspartic acid (polysuccinimide PSI) (confirmed by potentiometric analysis). At the beginning of the polycondensation, the media was observed to agglomerate, which was removed by scraping the reactants. Thereafter, the test was developed in a pulverulent medium without coagulation. The product had a viscosity index VI2 of 16.6 ml / g and the following Hunter color. L = 89.7 a = -0.5 b = 14.3

Example 9 (comparative) 50 g of L-aspartic acid and 25 g of 85% phosphoric acid are introduced into a 2 liter rotary evaporator flask. The reaction components are heated under atmospheric pressure to 180 ° C. (oil bath temperature) for 4 hours. The rotation speed of the flask is 90 rpm (the speed required to prevent foaming of the reaction medium; for example, the foam overflows from the flask at a low spin rate of 20 rpm). The formation of a viscous mesophase, slight swelling and subsequent solidification of the reaction medium was observed during the polycondensation operation.
The resulting reaction product is crushed in a mortar, then washed three times with 1.8 liters of water each, and then at 60 ° C. and 8000 Pa.
For 31 hours. 34.85 g of PSI were recovered (corresponding to a yield of 95.6%). The product is 11.
It had a viscosity index VI2 of 3 ml / g and the following Hunter color. L = 92.0 a = -0.3 b = 6.9

Example 10 (Comparative) 50 g of L-aspartic acid and 25 g of 85% phosphoric acid are introduced into a 2 liter rotary evaporator flask. The reaction components were brought to 180 ° C. (oil bath temperature) at 1300 Pa for 2 hours 3
Heat for 5 minutes. The rotation speed of the flask is 90 rpm (the speed required to prevent foaming of the reaction medium).
The formation of a viscous mesophase and subsequent solidification of the reaction medium was observed during the polycondensation operation. The reaction obtained is ground in a mortar and then washed three times with 1.6 l of water each time and then dried at 60 ° C. and 8000 Pa for 51 hours. 37.2 g of PSI were recovered (corresponding to a yield of 100%). The product had a viscosity index VI2 of 32.5 ml / g and the following Hunter color. L = 88.8 a = -0.0 b = 11.6

Continuation of front page (56) References JP-A-55-18474 (JP, A) JP-A-60-203636 (JP, A) JP-A-48-11990 (JP, A) JP-A-7-126379 (JP) JP-A-7-216084 (JP, A) JP-B-48-2038 (JP, B1) JP-B-39-20527 (JP, B1) JP-B-39-22610 (JP, B1) 43-8883 (JP, B1) JP-B-46-4190 (JP, B1) JP-B-48-7710 (JP, B1) French patent 2665166 (FR, B) (58) Fields investigated (Int. Cl. ⁶ , DB name) C08G 69/10 C08G 73/10 C07K 7/10

Claims (7)

(57) [Claims] 1. A method for producing a polycondensate of amino acids by bulk thermal polycondensation of at least one amino acid selected from aspartic acid and glutamic acid in the presence of phosphoric acid, phosphorus pentoxide or polyphosphoric acid as a polycondensation catalyst. A process for producing a finely divided powder comprising a catalyst, in which an amount of 0.005 to 0.25 mole, expressed as P atoms per mole of amino acid, is uniformly dispersed in the amino acid before starting the polycondensation reaction. Forming a polycondensation medium, wherein the polycondensation medium is subjected to the polycondensation without solvent in the form of a finely divided substance, and the polycondensation medium is kept in a finely divided state throughout the entire polycondensation operation. 2. The process according to claim 1, wherein the polycondensation operation is carried out at a temperature of from 150 to 220.degree. 3. A pulverulent substance to be formed before the polycondensation reaction is started:-a mixture of an amino acid and phosphoric acid or polyphosphoric acid is pasted with water, and water is removed by evaporation under atmospheric pressure or vacuum. By dissolving the amino acid and phosphoric acid or polyphosphoric acid in water, and then spraying the solution; by suspension of the amino acid in an aqueous solution of phosphoric acid or polyphosphoric acid By evaporating an aqueous solution of phosphoric acid or polyphosphoric acid on a fluidized bed of amino acids, or by co-milling or milling phosphorus pentoxide and amino acids. Claim 1 or 2
The described method. 4. The catalyst used is phosphoric acid or polyphosphoric acid, and the finely divided substances formed before the polycondensation reaction is started are:-introducing phosphoric acid or polyphosphoric acid into amino acids; Homogenizing by pasting with a sufficient amount of water to obtain a pasty medium; removing excess water from the mixture by drying at atmospheric pressure or under vacuum; The method according to claim 1, wherein the method is obtained by crushing an object. 5. A method for producing a polypeptide which is a hydrolyzate of a polycondensate of an amino acid by subsequently hydrolyzing the polycondensate of an amino acid obtained by the method according to any one of claims 1 to 4. . 6. The method according to claim 5, wherein the polyimide polycondensate obtained by the polycondensation is hydrolyzed into a polypeptide salt by adding a basic reagent. 7. The method according to claim 6, wherein the polypeptide salt is neutralized to a polypeptide acid by further adding an inorganic or organic acid to the obtained polypeptide salt.